Is SNRNP200 p.Ile1663Val (c.4987A>G) pathogenic?

SNRNP200 p.Ile1663Val (c.4987A>G) is classified Conflicting classifications of pathogenicity in SNRNP200 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-07). AlphaMissense: likely benign (0.0753); Very rare (popmax 0.00667%, afr); Associated with Inborn genetic diseases.

What condition is associated with SNRNP200 p.Ile1663Val (c.4987A>G)?

SNRNP200 p.Ile1663Val (c.4987A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SNRNP200 p.Ile1663Val (c.4987A>G) in the general population?

SNRNP200 p.Ile1663Val (c.4987A>G) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about SNRNP200 p.Ile1663Val (c.4987A>G)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

SNRNP200 p.Ile1663Val

c.4987A>G · rs372940792 · VCV1010710

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.79, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 11 kb · p 1.9e-29 · regional, not allelic
Overall
CADD	19.79	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,916 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000372% 6/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,983
Admixed American	0.00167%	60,016

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SNRNP200
Protein: p.Ile1663Val
Coding: c.4987A>G
MANE Select: NM_014014
dbSNP: rs372940792
Type: single nucleotide variant
Location: chr2:96281851 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.89 · 85 PDB
Residue 1663: a β-strand; the helicase c-terminal 2 domain; the 'interaction with c9orf78 and wbp4' region; the 'interaction with tssc4' region

Full SNRNP200 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SNRNP200 p.Ile1663Thr Likely benign ★ same residue
SNRNP200 p.Ala1675Thr Uncertain significance ★★ ⚠ same condition
SNRNP200 p.Ala1995Val Uncertain significance ★★ ⚠ same condition
SNRNP200 p.Ala402Thr Uncertain significance ★★ ⚠ same condition
SNRNP200 p.Arg1901His Uncertain significance ★★ ⚠ same condition
SNRNP200 p.Arg1973His Uncertain significance ★★ ⚠ same condition
SNRNP200 p.Arg1993Gln Uncertain significance ★★ ⚠ same condition
SNRNP200 p.Arg437Cys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/snrnp200-p-ile1663val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown